Abstract:
A method of treating a subject having or at risk for having a virus infection, by administering to the subject a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs, wherein the guide RNAs are complementary to two target sequences spanning from the 5′- to 3′-LTRs of the sequence in the virus. A method of treating a subject having or at risk for having a virus infection, by administering to the subject a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs, wherein the guide RNAs are complementary to two target sequences spanning from the 5′- to 3′-LTRs of the sequence in the virus, and causing neither genotoxicity nor off-target editing to the host.
Abstract:
A method of treating a subject having or at risk for having a virus infection, by administering a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs that are complementary to two target sequences spanning from the 5′- to 3′-LTRs of the sequence in the virus, and completely excising a fragment of greater than 9000-bp of integrated proviral DNA that spanned from its 5′- to 3′-LTRs. A method of treating a subject having or at risk for having a genetic caused disease, by administering a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs that are complementary to two target sequences spanning from the sequence of the subjects DNA greater than 9000-bp that is chromosomally integrated and causes the genetic caused disease, and excising the chromosomally integrated sequence.
Abstract:
A personalized method of inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus, by determining a nucleic acid sequence of the HIV-1 proviral DNA harbored by a subject, designing two or more different multiplex guide RNAs (gRNAs) complementary to the HIV-1 proviral DNA sequences in the subject, administering to the subject a therapeutically effective amount of a composition comprising a CRISPR-associated endonuclease, and the two or more different multiplex gRNAs, cleaving a double strand of the proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease, cleaving a double strand of the proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease, excising an entire HIV-1 proviral genome, and eradicating the HIV-1 proviral DNA from the host cell.
Abstract:
A method of immunizing a subject at risk of HIV-1 virus infection, by administering to the subject a prophylactically effective amount of a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different multiplex guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of proviral DNA of the virus that is unique from the genome of the host cell, cleaving a double strand of the proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease, cleaving a double strand of the proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease, excising an entire HIV-1 proviral genome, eradicating the HIV-1 proviral DNA from the host cell, and preventing HIV-1 virus infection in the subject.
Abstract:
A method of treating a subject having a retroviral infection, by administering to the subject a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs, wherein the guide RNAs are complementary to two target sequences spanning from the 5′- to 3′-LTRs of the sequence in the retrovirus, and eradicating the retroviral infection. A method of immunizing a subject at risk of retroviral infection, by administering a prophylactically effective amount of a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of proviral DNA of a retrovirus to the subject, and preventing retroviral infection in the subject.
Abstract:
The present disclosure relates to novel modular methods for generating a diversity of N-glycans of high mannose, hybrid and complex types. The present disclosure also relates to exemplary arrays of the synthesized N-glycans spotted onto aluminium oxide coated slides. These arrays can be used to detect and analyze binding interactions between the synthesized N-glycans and glycan binding molecules, such as HIV-1 neutralizing antibodies. The present disclosure also relates to methods for identifying agents that bind to various types of molecules on the arrays and to defining the structural elements of the molecules on the arrays that bind to those agents. The arrays and methods provided herein may be used for general epitope identification, drug discovery and as analytical tools. The present disclosure also provides useful glycans and epitope determinants that are useful in detecting, diagnosing, recurrence monitoring and preventing pathological diseases such as HIV.
Abstract:
Methods of using azide-modified biomolecules, such as fatty acids, carbohydrates and lipids, to treat a plant, an insect or an animal infected with a virus or to inhibit infectivity of a virus, such as the human immunodeficiency virus, are provided. Also provided are methods of labeling a virus, such as human immunodeficiency virus, with an azide-modified biomolecule, such as a fatty acid, a carbohydrate, or an isoprenoid lipid. Also, provided are methods of tracking a virus in vivo, with an azide-modified biomolecule, such as a fatty acid, a carbohydrate, or an isoprenoid lipid. The azide-modified biomolecules may be combined with a pharmaceutically acceptable excipient to produce a pharmaceutical composition, optionally containing another anti-viral agent and/or a delivery agent, such as a liposome.
Abstract:
The present invention relates to a method for reducing the occurance and/or severity of viral infections. The method embodies procedures for expanding HIV from the blood of HIV antibody negative donors and deriving a non-infectious virus particle product that is antigenic. The procedures for deriving the antigenic, non-infectious virus particle product are optimally designed to maintain the integrity of the envelope proteins while maximizing the depletion of capsid proteins and RNA. The resulting virus particle product, when introduced into humans or non-human animals, enables the production of antibodies that target the natural envelope macromolecular structure that is required for infectivity. The present invention can be applied to producing virus stocks from the blood of HIV-seronegative donors, for deriving non-infectious virus particles that retain intact envelope proteins, for producing anti-viral antibodies, and for administering anti-virus antibodies to patients.
Abstract:
The present invention discloses positive control material for nucleic acid amplification based detection of microorganisms in biological samples. The control material comprises purified microorganism that is rendered non-infectious but is amenable to nucleic acid amplification. Also disclosed is a process for making and using the control material.
Abstract:
The present invention relates to compounds that modulate ribosomal frameshifting and nucleic acid constructs for use in methods for identifying or validation of compounds that modulate ribosomal frameshifting. In particular, the present invention relates to the use of nucleic acid constructs to identify or validate compounds capable of modulating the efficiency of programmed ribosomal frameshifting and the use of compounds that modulate the efficiency of programmed ribosomal frameshifting to inhibit the replication or infectivity of viruses that employ programmed ribosomal frameshifting.